Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Study information

Scientific title

Efficacy and safety of growth hormone treatment in short children born small for gestational age; effects of growth hormone levels on growth, insulin sensitivity and body composition

Acronym

IUGR-3 study

Study hypothesis

Children born small for gestational age (SGA) might be at increased risk for developing hypertension, cardiovascular disease and diabetes mellitus type 2. It has been shown that those SGA children with relatively higher growth hormone (GH) levels during an overnight GH-profile had more signs of insulin resistance. GH treatment does not seem to increase the risk of these diseases, but insulin sensitivity has not yet been evaluated in detail and has not yet been studied in relation to age, body composition, and baseline serum levels of GH, insulin-like growth factor (IGF)-1 and IGF-binding proteins. This type of research is very important since it might give clues which children are more prone to developing metabolic syndrome in later life and whether GH treatment during childhood and puberty has any effect on the development of this metabolic syndrome.

Ethics approval

Not provided at time of registration

Study design

Randomised, parallel group, multicentre trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Small for gestational age (SGA), children with persistent short stature

Intervention

Growth hormone treatment Norditropin SimpleXx 15 mg/1.5 ml.The first 60 patients of five years and older who are included in the study, will undergo an overnight GH-profile, frequently sampled intravenous glucose tolerance test (FSIGT) and dual energy X-ray absorptiometry (DEXA). After stratification for gender, age, GH status, these patients will be randomised into two different groups: during the first six months, groups A and B will receive GH therapy in a dose of 1 and 2 mg/m^2/day, respectively. Subsequently, all patients will continue GH treatment with a dose of 1 mg/m^2/day.

Those patients of five years and older who will not undergo an overnight GH profile, FSIGT and DXA and all patients younger than 5 years will receive 1 mg GH/m2/day.

Intervention type

Drug

Phase

Not Specified

Drug names

Norditropin

Primary outcome measure

1. To determine before, during and after treatment termination of long-term growth hormone treatment:a. Insulin sensitivity (via frequent sampling intravenous glucose tolerance test)b. Body composition: in relation to each other and baseline serum GH levels during an overnight GH profile and in relation with six months of treatment with two different GH doses2. To assess the long-term efficacy of biosynthetic GH treatment in a dose of 3 IU/m^2/day on final height and other various auxological parameters

Secondary outcome measures

Overall trial start date

01/03/2002

Overall trial end date

01/10/2009

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Children born with a birth length and/or weight <2 standard devations (SD) for gestational age (Usher McLean)2. Neonatal period without signs of severe asphyxia (defined as Apgar score <3 after five minutes), and no serious diseases such as long-term artificial ventilation and oxygen supply, bronchopulmonary dysplasia or other chronic lung diseases3. Short stature defined as a height SD score below 2.5 according to the Dutch National Growth references of 19974. Height velocity (cm/year) for chronological age5. Chronological age at the start of treatment: 3.00 - 7.99 years (boys and girls)6. Prepubertal signs defined as Tanner stage 1 or testicular volume <4 ml7. Well documented growth data from birth up to two years and at least one year before the start of the study8. Both growth hormone deficient and growth hormone insufficient patients9. Informed consent

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

157

Participant exclusion criteria

1. Chromosomal disorders, known syndromes and serious dysmorphic symptoms suggestive for a syndrome that has not yet been described, except for Silver Russell syndrome2. Coeliac disease and other chronic or serious diseases of the gastrointestinal tract, heart, genitourinary tract, liver, lungs, skeleton, central nervous system, metabolic disease, chronic or recurrent major infectious diseases, nutritional and/or vitamin deficiencies3. Any endocrine or metabolic disorder such as diabetes mellitus, diabetes insipidus, hypothyroidism, or inborn errors of metabolism, except for growth hormone deficiency (GHD)4. Use of medications or interventions at this moment or during the previous six months that might have interfered with growth, such as corticosteroids (including high dose of corticosteroid inhalation), sex steroids, growth hormone, or major surgery (particularly of the spine or extremities)5. Active malignancy or increased risk of leukaemia6. Serious suspicion of psychosocial dwarfism (emotional deprivation)7. Expected non-compliance